New Era for Generic Drugs

The promise of the Generic Drug User Fee Amendments of 2012 (GDUFA) is to end multiyear reviews of new generic drugs and the ever-growing queue of pending applications. After years of resistance, generic-drug makers agreed last year to provide funds to FDA to support speedier approval of abbreviated new drug applications (ANDAs) and prior approval supplements (PASs), as well as timely inspection of domestic and foreign manufacturers and suppliers of APIs.

To launch the new fee program on Oct. 1, 2012, FDA issued a wave of Federal Register notices and guidance documents in August 2012 that officially inform manufacturers of relevant procedures and obligations. The various fees authorized by GDUFA will provide $299 million in funding for FDA in fiscal year 2013 and $1.5 billion over five years. Application fees of approximately $50,000 will add up to almost $100 million, primarily from payments on an expected 750 to 900 ANDAs each year, plus some 750 supplements. Approximately $15 million will be levied on newly referenced (type II) drug master files (DMFs) on a one-time basis according to a fairly complex process; an FDA Q&A guidance spells out specifics on this and other issues and how fees will be calculated (1).

IDENTIFYING FACILITIES

Approximately $175 million in fees will be levied annually on facilities operated by manufacturers of both finished dosage forms (FDFs) and API producers, the majority (approximately $140 million) collected for FDFs. The payments will be $15,000–$30,000 higher for foreign facilities to reflect added inspection costs, and plants that produce both finished drugs and APIs will pay both fees. One tricky issue is how to account for facilities with several buildings at one site. Such complexes may owe only one fee if FDA determines that the site can be inspected at one time, based on activities and ownership structure. But one company with several distinct facilities most likely will pay fees for each location.

This manufacturer "self identification" program expects to collect information from 3000 or so organizations, facilities, and sites utilizing existing electronic data submission processes and familiar file formats to reduce the data collection burden on the agency and industry (2). Manufacturers will provide Data Universal Numbering System numbers and Facility Establishment Identifiers plus physical addresses and contact details. Various producers have to register with FDA, but do not have to pay fees, including repackagers, manufacturers of positron emission tomography drugs, and sites conducting bioequivalence or bioavailability studies and other analytical testing.

In addition to determining who has to ante up, FDA expects the facility identification program will provide important information to promote global supply chain transparency. The data will go into new generic-drug facility databases, which will provide information to help FDA address global supply chain issues. Among other stated goals, FDA will conduct biennial GMP surveillance inspections of generic API producers and product manufacturers, with the aim to achieve parity in inspection frequency between foreign and domestic firms in 2017.